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Biomedical subjects

David J Hak

Publications and source records attributed to David J Hak.

12 recordsLinked to original sources

Recombinant human BMP-7 effectively prevents non-union in both young and old rats.

The purpose of this study was to evaluate the influence of age on the effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage that is known to result in non-union formation. Closed stabilized femur fractures were produced in 3-month-old and 18-month-old rats. The fracture site was exposed and 2 mm of the periosteum cauterized circumferentially to impair normal fracture healing. The cauterized fracture site was immediately treated with either 100 microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group). Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and histological evaluation. In both age groups, none of the control animals healed throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month-old animals were radiographically healed at 3 weeks. In comparison, only 56% (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals had healed. Histology revealed slower healing in the 18-month-old animals. Treatment with rhBMP-7 significantly increased all of the biomechanical properties in both age groups. In the 3-month-old animals the mechanical strength approached that of the intact femur at 3 weeks, while in the 18-month-old animals this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively stimulate fracture repair in both young (3-month-old) and old (18-month-old) rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater in young rats compared to old rats.

Aging↗

Effect of low molecular weight heparin on fracture healing in a stabilized rat femur fracture model.

The purpose of this study was to evaluate the effect of low molecular weight heparin (LMWH) on fracture healing in a standard stabilized rat femur fracture model. A closed, mid-diaphyseal transverse fracture was created in the right femur of Long-Evans rats after insertion of a 0.8-mm K-wire into the medullary canal. Animals were randomized to receive either LMWH (70 units/kg dalteparin) or an injection of normal saline daily for 2 weeks. Animals were sacrificed at 2, 3, and 6 weeks. Fracture healing was assessed by radiographs, histology, and mechanical testing. There were no significant differences between the control and LMWH groups in the percentage of animals with radiographic bridging callus at each time point. Histologic appearance of fracture healing was similar between the control and LMWH groups. There were no significant differences in the normalized mechanical properties of the control and LMWH groups at 2 and 3 weeks. At 6 weeks, the percent torque of the LMWH group was significantly greater than the control group ( p = 0.0072), however, there was no significant difference in the stiffness and energy absorption. Dalteparin, at the dosage used in this study, did not impair fracture healing in this standard stabilized rat femur fracture model.

Animals↗

Global gene profiling reveals a downregulation of BMP gene expression in experimental atrophic nonunions compared to standard healing fractures.

Nonunion is a challenging problem that may occur following certain bone fractures. However, there has been little investigation of the molecular basis of nonunions. Bone morphogenetic proteins (BMPs) play a significant role in osteogenesis. However, little is known about the expression patterns of BMPs in abnormal bone healing that results in nonunion formation. These facts prompted us to investigate and compare the gene expression patterns of BMPs and their antagonists in standard healing fractures and nonunions using rat experimental models. Standard closed healing fractures and experimental atrophic nonunions produced by periosteal cauterization at the fracture site were created in rat femurs. At postfracture days 3, 7, 10, 14, 21, and 28, total RNA was extracted from the callus of standard healing fracture and fibrous tissue of nonunion (n=4 per each time point and each group). Gene expression of BMPs, BMP antagonists, and other regulatory molecules were studied by methods including Genechip microarray and real-time quantitative RT-PCR. Gene expression of BMP-2, 3, 3B, 4, 6, 7, GDF-5, 7, and BMP antagonists noggin, drm, screlostin, and BAMBI were significantly lower in nonunions compared to standard healing fractures at several time points. Downregulation in expression of osteogenic BMPs may account for the nonunions of fracture. The balance between BMPs and their endogenous antagonists is critical for optimal fracture healing.

Animals↗

High-energy proximal tibial fractures: treatment options and decision making.

High-energy proximal tibial fractures are complex injuries with significant associated soft-tissue damage. There is a high percentage of open injuries, compartment syndrome, and vascular injuries in patients with these fractures. These patients usually have significant articular depression, excessive comminution, condylar displacement, and metadiaphyseal extension of the fracture. Management of these complex injuries requires treatment of the soft tissues and bony components. Surgical treatment of these injuries traditionally has been associated with substantial complications such as infection, knee stiffness, malunion, loss of fixation, soft-tissue failure, and amputations. Staged treatment, with initial application of a spanning external fixator followed by definitive fixation, has been used in recent years to decrease the risk and rate of complications. Definitive fixation may be performed using traditional open approaches or percutaneously or an external fixator may be used. Development of a protocol for treating these injuries must be done to allow optimal fracture and patient outcomes.

Decision Making↗

The effectiveness of standard povidone iodine surgical preparation in decontaminating external fixator components.

The purpose of this study was to evaluate the effectiveness of standard iodine surgical scrubs to remove bacteria from external fixator components. Sterile adjustable external fixation clamps, Schanz pins, and carbon fibre rods were coated with a sterile protein solution and immersed in solution of coagulase negative Staphylococcus (10(3)organisms/ml). They were then decontaminated in standard fashion using a povidone iodine scrub and paint solution. After neutralisation the components were sonicated, serially diluted, plated on blood agar, and incubated for 24h. Unassembled external fixation components were examined individually, and as assembled pin-rod-clamp constructs with and without manipulation of the clamp. Of the three external fixation components (pins, rods, clamps) the highest number of bacterial colony forming units was seen on the external fixation clamps. Manipulation of the assembled construct significantly increased the mean bacterial colony counts compared to the assembled non-manipulated construct (p=0.0007). Standard surgical preparation does not remove all bacteria from external fixators during subsequent operative procedures.

Anti-Infective Agents, Local↗

Coronal fractures of the distal femoral condyle: a biomechanical evaluation of four internal fixation constructs.

This study evaluated different fixation methods in posterior femoral condyle coronal fractures. A standardised osteotomy was created in synthetic composite femurs and fixed with one of four methods (one 3.5 mm diameter screw, two 3.5 mm screws, one 6.5 mm screw, two 6.5 mm screws). The stiffness and mean loads to specified displacements were measured. The stiffness of two 6.5 mm screws was significantly greater than both single 3.5 mm screw (3567 versus 2584N/mm; p=0.0075) and double 3.5 mm screws (3567 versus 2080N/mm; p=0.003). There was no statistical difference in the stiffness of one 6.5 mm screw compared to either the single or double 3.5mm screws. Increasing the screw diameter and using two screws increased the load at 1, 2 and 3 mm of displacement. In the fixation of posterior femoral condyle fractures, two 6.5 mm screws are more rigid than either single or double 3.5 mm screws. The use of a second screw marginally increases the rigidity of fixation. If 3.5 mm screws are used in the fixation of posterior femoral condyle fractures, at least two screws should be used to approximate the biomechanical stability of a single 6.5 mm screw.

Biomechanical Phenomena↗

Prevention of atrophic nonunion development by recombinant human bone morphogenetic protein-7.

Severe periosteal and soft tissue disruption at the time of fracture may result in the formation of an atrophic nonunion. We have developed a reproducible atrophic nonunion in an animal model. The purpose of this study was to evaluate whether the immediate application of recombinant human BMP-7 to the fracture site could rescue the healing process in this nonunion model. A total of 56 three month old Fisher 344 rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three point bending device. To create a nonunion, the fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. The fracture site was immediately treated with either the application of rhBMP-7 50 microg in 25 microl of rat tail tendon collagen buffer (BMP-7 group), or with 25 microl of rat tail tendon collagen buffer only (Control group). Fracture healing was evaluated with serial radiographs every two weeks for an eight weeks period. Specimens at four and eight weeks were subjected to biomechanical and histological evaluation. None of the Control group healed throughout the eight weeks experimental duration. At four weeks 63% of the BMP-7 group had healed, and all had healed by six weeks. This investigation showed pronounced differences between the BMP-7 group and the Control group both histologically and biomechanically. In conclusion, we have demonstrated that the immediate application of BMP-7 may rescue the fracture healing process and prevent the development of nonunion following severe periosteal disruption.

Animals↗

The role of pelvic angiography in evaluation and management of pelvic trauma.

Controversy exists about the indications and optimal timing of angiography in hemodynamically unstable patients with severe pelvic fractures. Recommendations from published studies are limited by small numbers of patients. In this article the recommended indications, timing, and drawbacks to angiography are reviewed.

Angiography↗

Pelvic fracture patterns and their corresponding angiographic sources of hemorrhage.

The association between pelvic arterial injuries and associated fracture patterns has been investigated directly in a post mortem study and indirectly in an earlier clinical study evaluating an overall management approach to pelvic fractures. One previous report has correlated the angiographic findings of a group of patients with pelvic ring disruptions. The authors' study was designed to further define the anatomic sites of hemorrhage associated with specific pelvic ring injury patterns and evaluate patient survival in each of these groups.

Aged↗

Preliminary stabilization of the less invasive stabilization system.

We describe the use of a universal T-handle chuck to provide preliminary stabilization of the Less Invasive Stabilization System supracondylar femur implant and aiming device. This technique is helpful to maintain the position of the plate against the bone during intraoperative radiographs and initial screw insertion. Use of this simple technique may help avoid the problems that occur when the plate is positioned too far away from the lateral femoral cortex.

Bone Plates↗

Development of an atrophic nonunion model and comparison to a closed healing fracture in rat femur.

Although most fractures heal, some fail to heal and become nonunions. Many animal models have been developed to study problems of fracture healing. The majority of nonunion models have involved segmental bone defects, but this may not adequately represent the biologic condition in which nonunions clinically develop. The objective of the present study is to develop a nonunion model that better simulates the clinical situation in which there is soft tissue damage including periosteal disruption and to compare this model to a standard closed fracture model utilizing identical fracture stabilization, providing a similar mechanical environment. A total of 96 three month old Long Evans rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three-point bending device. To create a nonunion, 48 of the rats received additional surgery to the fractured femur. The fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. Fracture healing was evaluated with serial radiographs every two weeks. Animals were maintained for intervals of two, four, six or eight weeks after surgery. Specimens from each time interval were subjected to biomechanical and histological evaluation. None of the cauterized fractures healed throughout the eight weeks experimental duration. The radiographical appearance of nonunion models was atrophic. This investigation showed pronounced differences between the experimental nonunions and standard closed fractures both histologically and biomechanically. In conclusion, we have developed a reproducible atrophic nonunion model in the rat femur that simulates the clinical condition in which there is periosteal disruption but no bone defect.

Animals↗

Lower extremity traction pins: indications, technique, and complications.

The placement of pins in the lower extremity for the purpose of skeletal traction is a basic skill required by an orthopedic surgeon. These pins are primarily used for the management of fractures and dislocations. Although simple, the insertion and care of these pins can be accompanied by severe complications including damage to neurovascular structures, physeal injury, ligamentous insult, fracture, and infection. We review the techniques of pin insertion at the distal femur, proximal tibia, and calcaneus to provide a foundation for residents and attendings alike so that unnecessary complications may be avoided and proper placement ensured.

Bone Nails↗